The protective effect of exenatide on the renal injury in diabetic rats

doi:10.12047/j.cjap.5466.2017.033

Abstract

Abstract: Objective: To investigate the protective effect of exenatide (Ex) on the renal injury in streptozotocin-induced diabetic rats. Methods: Sprague-Dawley rats were randomly divided into 2 groups:normal control group (NC group, n=8) and model group. Model group was injected with low dose of streptozotocin (30 mg·kg^-1) after the rats were fed with high fat and high glucose diet for 4 weeks. Seventy-two hours later, rats of blood glucose level ≥ 16.7 mmol·L^-1 were divided into diabetes mellitus group (DM, n=10) and two exenatide-treated groups (Ex groups,3 or 6μg·kg^-1, n=8). Ex groups subcutaneously injected with exenatide for 12 weeks, but NC group and DM group were injected with the same volume of solvent. Changes in glycolipid metabolism and renal function such as serum creatinine (Scr), urine creatinine (Ucr), blood urea nitrogen (BUN), 24 hour urine micro-albumin (24 h UMA)in the 4 groups of rats were determined and creatinine clearance rate (Ccr) were calculated. Renal oxidative stress parameters such as superoxide dismutase (SOD), malondialdehyde(MDA), glutathione per-oxidase (GSH-Px) were measured. Hematoxylin-eosin (HE) staining was used to examine pathological morphology in the renal tissues and ELISA was performed to determine the level of advanced glycation end products(AGEs), the glycosylation end product in renal tissues. Results: Compared to the DM group,glycolipid metabolic abnormalities in the exenatide-treated groups were significantly ameliorated with lower levels of blood glucose,HbAlc, cholesterol and triglyceride (P < 0.05). The renal function index was markedly improved (P < 0.05) with Ccr reduced, indicating a high glomerular filtration status. Meanwhile, exenatide treatment improved the diabetes-induced pathological changes in renal morphology, substantially increased the activities of SOD and GSH-Px, and reduced the levels of MDA and AGEs. Conclusion: Exe-natide has the renal protective effect probably by the mechanisms of inhibition of AGEs production and reduction of oxidative stress in the renal tissues of diabetic rats.

Key words: exenatide, diabetes nephropathy, advanced glycation end products, oxidative stress

HUANG Qiong-zhu, LIU Xiao-meng, HUANG Guo-quan, WANG Li-juan, ZHENG Yu-jie, CHEN Xin-cheng, LIU Li-bin, CHEN Zhou. The protective effect of exenatide on the renal injury in diabetic rats[J]. CJAP, 2017, 33(2): 128-131.

References

[1] Kitada M, Kanasaki K, Koya D. Clinical therapeutic strate-gies for early stage of diabetic kidney disease[J]. World J Diabetes, 2014, 5(3):342-356.
[2] 齐敏友, 杨钧杰, 周斌, 等. 熊果酸对糖尿病小鼠肾病的保护作用及机制研究[J]. 中国应用生理学杂志, 2014, 30(5):445-448.
[3] Yamagishi S. Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes[J]. Exp Gerontol, 2011, 46(4):217-224.
[4] Skov J. Effects of GLP-1in the kidney[J]. Rev Endocr Metab Disord, 2014, 15(3):197-207.
[5] Gedulin BR, Nikoulina SE, Smith PA, et al. Exenatide (exendin-4) improves insulin sensitivity and β-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight[J]. Endocrinology, 2005, 146(4):2069-2076.
[6] Panchapakesan U, Mather A, Pollock C. Role of GLP-1and DPP-4in diabetic nephropathy and cardiovascular disease[J]. Clin Sci (Lond), 2013, 124(1):17-26.
[7] 李颖萌, 范雪梅, 王义明, 等. 葛根芩连汤对2型糖尿病大鼠的治疗作用及其机制探讨[J]. 药学学报, 2013, 48(9):1415-1421.
[8] Nielsen LL, Young AA, Parkes DG. Pharmacology of exe-natide (synthetic exendin-4):a potential therapeutic for im-proved glycemic control of type 2diabetes[J]. Regul Pept, 2004, 117(2):77-88.
[9] Xu WW, Guan MP, Zheng ZJ, et al. Exendin-4alleviates high glucose-induced rat mesangial cell dysfunction through the AMPK pathway[J]. Cell Physiol Biochem, 2014, 33(2):423-432.
[10] Fujita H, Morii T, Fujishima H, et al. The protective roles of GLP-1R signaling in diabetic nephropathy:possible mech-anism and therapeutic potential[J]. Kidney Int, 2014, 85(3):579-589.
[11] Tesch GH, Lim AK. Recent insights into diabetic renal in-jury from the db/db mouse model of type 2diabetic nephropa-thy[J]. Am J Physiol Renal Physiol, 2011, 300(2):F301-310.
[12] 杨锐, 刘小粉, 马善峰, 等. 硫化氢对1型糖尿病大鼠肾脏的保护作用[J]. 中国应用生理学杂志, 2016, 32(2):181-184.

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